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Home , Camphor, Thymol

Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology

ISSN: 0975-766X CODEN: IJPTFI Available Online through Research Article www.ijptonline.com FORMULATION AND EVALUATION OF STABILITY FOR TOPICAL GEL USING EUTECTIC MIXTURE WITH NATURAL GELLING AGENT Dr. Shweta P. Ghode*, Mrs. Vibhavari M. Chatur, Dr. Sanjay R. Chaudhari, Mr. Rohit Nalawade, Ms. Rekha Barpha, Ms. Srushti Doshi Rasiklal M. Dhariwal Institute of Pharmaceutical Education and Research, Chinchwad, Pune-19. Email: [email protected] Received on: 02-11-2018 Accepted on: 05-12-2018

Abstract

Eutectic system is a mixture or solution which the ingredients solidify or liquefy simultaneously. A eutectic mixture is therefore that unique composition of two (or more) components that has the lower crystallization temperature or .1

Thymol, and are well known in the materia medica of western medicine as well as in that of the indigenous medicine in . has been considered important as powerful , germicidal and anthelmintic properties. Menthol is extensively employed in liniments, spraying lotions and in dental practice.

Camphor is one of the commonest remedies used in every household in India for a variety of purposes. 2

This study was conducted to develop a gel formulation of Eutectic mixture of Thymol, Menthol and Camphor using two natural gelling agents in different formulations, such as Astragalus gummifer L. (Tragacanth) and

Wild Acacia arabica (Acacia) resp. and evaluate its stability. The gel formulation was designed using Carbopol,

Sodium alginate, Isopropyl paraben, Glycerin and Water. The gel was formulated using accurately weighted amount of extract along with other additives, poured into the fixed amount of Carbopol 934 dispersion with constant stirring. The herbal gel formulations prepared were subjected to preliminary evaluation such as color, homogeneity, consistency, pH, Spreadability, Drug content uniformity, Viscosity and Stability. The parameters were found to be satisfactory. Stability studies showed that physical appearance, rheological properties remained unchanged upon storage for two months at ambient temperature. The Gel-formulation containing Tragacanth showed good Spreadability, Consistency and Stability than Acacia.

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology Key words: Acacia arabica (Acacia), Astragalus gummifer L. (Tragacanth), Camphor, Menthol, Thymol.

Introduction:

GEL is nothing but the semi- dosage forms which are highly viscous and consist organic polymer and gelling agent. Eg. Topical gel, Hair gel. Man has always been plagued with ailments and diseases of both the body and the mind. However dedicated research from scientists all over the world has made it possible to treat, prevent and eradicate many of these diseases that plague man (3, 4). The field of pharmaceutical science has been developing steadily over the years, and has today become invaluable in helping to keep us healthy and prevent disease. An avenue of research that has progressed a great deal in the past few decades is the treatment of diseases via biomolecules such as drugs, proteins etc. Initially these could only be administered in limited manner, due to limitations of drug delivery through harmful environments in the body (4, 5). Thus limited mobility reduced the effectiveness of administered drugs. Progress came with the development of carriers which could be encapsulated, or immobilized with drugs, allowing the drug to safely reach the required site without harm. These carriers allowed for the release of drug in sites which were previously inaccessible. The nature of these carriers progressed over the years from ceramics, to natural, to synthetic materials. Factors such as integrity, biocompatibility and flexibility were considered, and lead to the use of three dimensional matrices as carrier materials (6). These are a class of materials are known as gels. These three dimensional polymer matrices are capable of imbibing large amounts of water, and biological fluids (7). This property of gels is the reason behind its varied applications ranging from food additives to pharmaceuticals and clinical applications

(8).

Topical Drug Delivery Systems:

Topical preparations are used for the localized effects at the site of their application by virtue of drug penetration into the underlying layers of skin or mucous membranes. The main advantage of topical delivery system is to bypass first pass metabolism. Avoidance of the risks and inconveniences of intravenous therapy and of the varied conditions of absorption, like pH changes, presence of enzymes, gastric emptying time are other advantage of topical preparations. Topical drug delivery can be defined as the application of a drug containing formulation to the skin to directly treat cutaneous disorders (e.g. acne) or the cutaneous

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology manifestations of a general disease (e.g. psoriasis) with the intent of confining the pharmacological or other effect of the drug to the surface of the skin or within the skin. Topical activities may or may not require intra- cutaneous penetration or deposition (9, 10). Topical drug delivery systems include a large variety of pharmaceutical dosage form like semisolids, liquid preparation, sprays and solid powders. Most widely used semisolid preparation for topical drug delivery includes gels, creams and ointments.

Use of Drugs:

1. Menthol:

Menthol is an organic compound made synthetically or obtained from corn mint, peppermint, or other mint oils.

It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above.

Uses: As an to reduce itching.

 As a topical ,

 It is used to relieve minor aches and pains, such as muscle cramps, sprains, headaches

 As a penetration enhancer in transdermal drug delivery.

 In certain medications used to treat sunburns, as it provides a cooling sensation

2. Thymol: (also known as 2-isopropyl-5-methylphenol, IPMP)

It is a natural monoterpenoid derivative of cymene, C10H14O, isomeric with , found in oil of , and extracted from Thymus vulgaris (common thyme) and various other kinds of plants as a white crystalline substance of a pleasant aromatic and strong antiseptic properties. Thymol also provides the distinctive, strong flavor of the culinary thyme, also produced from T. vulgaris.

Uses:

 Thymol has been used in solutions and in dusting powders for the treatment of tinea or ringworm and to treat hookworm infections.

 It is also used as a in , an anaesthetic, and as an antiseptic in .

 When used to reduce plaque and , thymol has been found to be more effective when used in

combination with than when used purely by itself.

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology  Thymol is also the active antiseptic ingredient in some toothpastes,

 Thymol has been used to successfully control varroa mites and prevent fermentation and the growth

of in colonies.

 lt is also used as a rapidly degrading, non-persisting .

 Thymol can also be used as a medical and general purpose disinfectant.

2. Camphor

Camphor is a waxy, flammable, transparent solid with a strong aroma. It is a with the chemical formulaC10H16O. It is found in the wood of the camphor laurel ( camphora), a large evergreen found in . It is used for its scent, as an ingredient in cooking (mainly in India), as an fluid, for medicinal purposes, and in religious ceremonies. A major source of camphor in Asia is camphor (the parent of ).

Uses

 Relieves Skin Itching And Irritation

 Alleviates Pain

 Soothes Burns

 Cures Acne

 Treats Eczema

 Cures Nail Fungus

 Good For Filling Up Cracked Heels

 Soothes Skin Rashes

 Fungal And Bacterial Infections

Materials: Thymol, menthol and camphor, Eutectic mixture, Astragalus gummifer L. (Tragacanth), Acacia arabica (Acacia), Carbopol, Sodium alginate, Isopropyl paraben, Glycerin and Water.

Equipment’s: Digital balance Shimadzu Corporation, Japan, pH meter, Magnetic stirrer, Water bath shaker

(Servell Instruments and Equipments Pvt. Ltd. Bangalore, India), Brookfield Viscometer (Brookfield

Engineering Laboratories, Inc. USA).

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology Methods:

Preparation of Eutectic mixture:

One systems of liquid eutectic were prepared by physical mixing of thymol, menthol and camphor (1:1:1). The physical appearance of them was evaluated which clear liquid mixtures obtained at room temperature were selected for next evaluations.

Preparation of Gel:

Ist formulation:

Mix tragacanth and glycerin properly with small quantities of water. Add carbopol with constant stirring if necessary add small quantity of water. Dissolve small quantity of sodium alginate in water and then add the paste. Remove moisture from formulation by using hot air oven. Add preservative. At the end, add eutectic mixture and store at R.T.

IInd formulation:

Mix acacia and glycerin properly with small quantities of water. Add carbopol with constant stirring if necessary add small quantity of water. Dissolve small quantity of sodium alginate in water and then add the paste. Remove moisture from formulation by using hot air oven. Add preservative. At the end, add eutectic mixture and store at R.T.

Storage: Store in cool and dry place at 35 -370c.

Container: Wide mouth bottle or collapsible tube.

Direction for use:

 This gel applies topically.

 Gel applies on the skin with the help of fingers.

 Gel applies on skin where inflammation causes with smooth hands.

 Do not rub this gel after applying it.

 Do not apply on .

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology Formula:

Sr. Ingredients Formulation 1 Formulation 2 No. (Tragacanth) (Acacia) 1. Eutetic mixture of Thymol, 1ml 1ml menthol and Camphr 2. Carbopol 0.8gm 0.8gm 3. Sod. alginate 3.3 gm 3.3 gm 4. Tragacanth 1gm - 5. Acacia - 1gm 6. Isopropyl paraben 0.03gm 0.03gm 7. Water q.s. q.s. 8. Glycerin 8 ml 9 ml

Stability study

For the evaluation of stability study, maintaining the formulations at an ambient condition over a period of two months. The physical appearance, pH value, drug content, rheological properties, drug release studies were determined periodically after the 1st and 2nd month after topical gel preparations.

Physical Examination:

Sr. Parameters Formulation 1 Formulation 2 No. (Tragacanth) (Acacia) Organoleptic Characteristics

1. Appearance Clear Not Clear

2. Color Light Brown Light Brown

3. Texture Smooth Sparingly Smooth

4. Odor Characteristic Characteristic

5. Nature Weak Acidic Weak Acidic

Physicochemical Characteristics

6. pH 4.5-5.2 5.2-5.3

7. Viscosity 1288.76CP 1168.44CP

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology General Characteristics

8. Spreadability Good Poor

9. Stability Good Poor

10. Grittiness No No

11. Moisture Content 12 % 10 %

12. Density 1.04 gm/cm3 1.10 gm/cm3

Results and Discussion:

Comparative study of Two Formulations

PARAMETERS 1st formulation 2nd formulation

Appearance Clear Small amount of lumps form

Base Easy to form Constant stirring needed

Thickener (carbopol) Easy to disperse Not easy to disperse

Moisture content Less More

Thickener Required in less amount Required in large amount

(Sod. Alginate)

Stability Good acacia swell in open

environment

Formulation

Conclusion:

From above results, we can conclude that Eutectic mixture of Thymol, Menthol and Camphor using two natural gelling agents in different formulations, such as Astragalus gummifer L. (Tragacanth) and Wild Acacia arabica

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology (Acacia) resp. showed acceptable physical properties concerning color, homogeneity, consistency,

Spreadability, Stability and pH value.

Among both the gel formulations, formulation 1st containing Tragacanth showed better Stability, pH,

Spreadability, Appearance, Color and Odor than 2nd containing Acacia. Also, formulation 1st showed better consistency, free from grittiness, non-staining, easy to remove and easy to wash, mainly non-irritating and easy to apply.

Where as in formulation 2nd containing Acacia we found the lumps formation on stability, ununiform

Spreadability and little skin itching on application.

Stability studies in both the gel formulations showed that, the physical appearance, drug content, pH, rheological properties remain unchanged upon storage for two months.

However In vitro Diffusion studies and Drug polymer Compatibility studies are required for further studies to evaluate the potential of the herbal gel formulation. In additional In vivo models are also required for further studies to use in clinical applications.

Carbopol gels shows superior drug release after that Na CMC, HPMC and sodium alginate shows decreasing order of drug release. In carbopol gel formulations, the drug release was decrease with increase in carbopol concentration because polymer concentration increases, viscosity increases. Viscosity is negatively related to the release of active substance () from formulations. All gel formulations containing penetration enhancer (propylene glycol) were used at different concentrations (5 to 10%), among them formulations containing 5% propylene glycol showed higher flux (permeability and drug release) values.

The research work was carried out to develop a new topical herbal gel formulation for topical application. The prepared herbal gel was further evaluated for pH, Viscosity and extrudability, Spreadability.

According to this comparative study, it has been conclude that, formulation 1st is better than 2nd because formulation 1st containing Tragacanth showed better stability, pH, Spreadability, appearance, color and odor.

Also, it showed better consistency, free from grittiness, non-staining, easy to remove and easy to wash, mainly non-irritating and easy to apply.

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology Where as in formulation 2nd containing Acacia we found the lumps formation on stability, ununiform

Spreadability and little skin itching on application.

However In vitro Diffusion studies and Drug polymer Compatibility studies are required for further studies to evaluate the potential of the herbal gel formulation. In additional In vivo models are also required for further studies to use in clinical applications.

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Dr. Shweta P. Ghode*et al. /International Journal of Pharmacy & Technology 10. Gisby J, Bryant J, Efficacy of a new cream formulation of mupirocin: Comparison with oral and topical

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Correspondence Author: Dr. Shweta P. Ghode1*. Email: [email protected]

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